The former San Francisco 49er superstar has unveiled the ad on Twitter.
Nike announced that Kaepernick will be a major part of its 30th anniversary "Just Do It" campaign.
The campaign featuring the former 49er reads: "Believe in something, even if it means sacrificing everything," alluding to his kneeling protest over social injustice.
A giant billboard featuring Kaepernick has been placed prominently on top of Nike's flagship just off Union Square in San Francisco.
Nike stocks rebounded a bit Wednesday morning following a dramatic dip after the announcement of the campaign.
President Donald Trump weighed in, saying Nike is getting "killed." Trump said on Twitter on Wednesday, "Just like the NFL, whose ratings have gone WAY DOWN, Nike is getting absolutely killed with anger and boycotts. I wonder if they had any idea that it would be this way?"
Trump has repeatedly slammed NFL players for kneeling in protest during the national anthem and says he'll find it difficult to watch the NFL "until they stand for the FLAG!"
Others, including Lebron James, say they're proud of Nike.
RELATED: Colin Kaepernick featured in Nike 'Just Do It' ad
Kaepernick already had a deal with Nike that was set to expire, but it was renegotiated into a multiyear deal to make him one of the faces of Nike's 30th anniversary "Just Do It" campaign, according to a person familiar with the contract. The person spoke to The Associated Press on condition of anonymity because Nike hasn't officially announced the contract.
Nike also provides all NFL teams with game-day uniforms and sideline apparel, a partnership that was extended in March to run through 2028.
Last week, Kaepernick scored a legal victory in his grievance against the NFL and its 32 teams when an arbitrator allowed his case to continue to trial. The quarterback claims that owners conspired to keep him out of the league because of his protests of social injustice..
Meanwhile, the league and players union still haven't resolved whether players will be punished this season if they choose to kneel or demonstrate during the national anthem. Owners approved a policy requiring players to stand if they are on the sideline during "The Star-Spangled Banner," allowing them to stay off the field if they wish.
But the league and union put that on hold after the Miami Dolphins faced backlash for classifying the protests as conduct potentially detrimental to the team - putting players at risk of fines or suspensions.
The Associated Press contributed to this report.